Use of collagen for the treatment of degenerative articular processes

ABSTRACT

The invention relates to the use of collagen for the production of a drug for the treatment of degenerative articular processes. An injection suspension is preferably produced, which contains collagen and possibly a local anaesthetic. This injection suspension is applied into the affected joints by means of an injection.

[0001] The invention relates to the use of collagen for the treatment ofdegenerative articular processes.

[0002] The basic type of degenerative, non-inflammatory joint diseasesis arthropathy or Arthrosis deformans in old age. Squat-bodied humanbeings, more men than women, after the 50th year are mainly affected.The condition begins slowly, but also progresses intermittently and atthe beginning without pain. The joints are only tender upon certainmovements. Avoiding strain on the joints promotes the progression of thecondition, but exercise and massages afford relief. Good successes canalso be achieved by the treatment with ultra-short waves.

[0003] Further therapies, which have been customary so far, are thesystematic administration of non-steroidal antirheumatic agents andpossibly intra-articular injections of agents for the protection ofcartilage, homoeopathic agents, local anaesthetics or cortisone.However, these therapies have the disadvantage that the destruction ofthe joints occurring finally due to degenerative joint processes cannotbe prevented, but only delayed, since the new formation of synovialfluids, such as mucopolysaccharides, cannot be stimulated, and nosynovial fluid is introduced into the affected joint from the outside.

[0004] Reconstituted type II collagen can be used for the detection ofantibodies against intact type II collagen in the blood in the case ofarthrorheuinatism (JP-A 62-012 800).

[0005] Collagens are long-fibred, linear-colloid, highly molecularscleroproteins of the extracellular matrix, which are found inconnective tissues (e.g. skin, cartilage, sinews, ligaments and bloodvessels), in the protein-containing ground substance of the bone(ossein) and in dentin together with proteoglycans. With a share of 25to 30% they are considered to be the quantitatively most frequent animalproteins. The structural basic unit of collagen, the tropocollagen (MWapprox. 300,000), consists of three polypeptide chains in the form ofspecial left-wound helices which, in turn, are righthandedly twistedaround one other according to the technique known in ropery (triplehelix). The tropocollagen molecule is a “rope” with a length of 280 nmand a diameter of 1.4 nm; the fibrils have a cross-section of 200 to 500nm (see Römpps Chemielexikon, vol. 3, page 2297, 1990).

[0006] As opposed to most proteins of the animal body, the collagens arenot continuously renewed. Once they are formed, they do not participatein the metabolism any more and age due to regular increase incross-linking due to the formation of hydrogen bridge bonds, ester bondsof amino acid residues with sugar residues and of isopeptide bondsbetween long-chain amino acid chains.

[0007] Modified collagen is used in medicine as a temporary skinreplacement, as a replacement for cornea and vitreous humour of the eye,as a replacement for sinews, synovial sheaths, hollow organs and bloodvessels, as a blood plasma substitute and in wound healing (EP-B 52288,JP-A-52-076 416). Collagen sponge is i.a. used as a haematostatic.Collagen containing drugs are used to improve dilatatable deformationsof the skin as they occur in scars, in skin atrophy caused by variouscauses and in skin creases caused by age. These collagen-containingdrugs are injected under the skin areas to be filled and, for thisreason, contain, as a rule, a local anaesthetic.

[0008] It is the object of the present invention to produce a drug forthe therapy of degenerative articular processes which does not have theaforementioned disadvantages.

[0009] This object is attained according to the invention by usingcollagen for producing a drug for the treatment of degenerativearticular processes.

[0010] The used collagen is unsoluble collagen, which can e.g. beobtained from calf and bovine skin; however, collagen from bovine skinis preferred.

[0011] The collagen is preferably contained in an injection suspension,particularly preferred in an amount of about 20 to 50 mg/ml. Theinjection suspension is applied by means of injection into the jointsaccording to the invention in the case of degenerative articulardiseases such as arthrosis or activated arthrosis. For this reason, alocal anaesthetic such as bupivacaine or lidocaine is preferablycontained. Lidocaine is contained with particular preference. Thepreferred amount of the contained local anaesthetic is 1 to 5 mg/ml.

[0012] As opposed to former therapies, the intraarticular use ofcollagen according to the invention in a drug has the advantage that itpromotes the lubrication process which only takes place insufficientlyin an arthrosis due to its properties, without attacking any substances,i.e without causing a damage.

[0013] “Carrier substances”, e.g. agents for the protection of cartilagecan be included in the collagen as a secondary element.

[0014] Examples of such agents for the protection of cartilage are thepreparations Dona 200 (active substance: D-glucosamine) and Dona 22S(active substance: D-glucosamine sulfate) and the homoeopathic agentsZeel and Heel.

[0015] The homoeopathic agent has the following composition:

[0016] 2.2 ml contain: extract (1:10) from Cartilago suis 22 ng, extract(1:10) from Funiculus umbilicalis suis 22 ng, extract (1:10) from Embryosuis 22 ng, extract (1:10) from Placenta suis (hormone-free) 22 ng, Rhustoxicodendr. φ 0.2 mg, arnica φ 0.2 mg, Dulcamara φ 0.22 μg, Symphytum φ22 μg, Sanguinaria φ 33 μg, sulphur φ 39.6 μg, Nacid 0.22 ng, coenzyme A0.22 ng, (±)-a-liponic acid, 0.22 ng, sodium oxalic acetat 0,22 ng.Moreover, the drug can still be slightly tinted, e.g. with compatibledyes.

[0017] The following examples explain the invention.

EXAMPLES 1 to 5

[0018] Various compositions of the active substance combination in theinjection suspension are indicated in the following examples. 1 ml ofinjection suspension containing: 1.  20 mg of collagen from calf skin  2 mg bupivacaine; 2.  30 mg of collagen from bovine skin   2 mg ofbupivacaine; 3.  35 mg of collagen from bovine skin   3 mg of lidocaine;4.  40 mg of collagen from bovine skin   3 mg of lidocaine; 5.  50 mg ofcollagen from calf skin 3.5 mg of bupivacaine.

Application Example 1

[0019] A young women, 32 years old, with therapy-resistant gonalgia, wastreated about 1½ years ago with injections of 0.5 ml of thecollagen-containing injection suspension according to example 3intraarticularily into the joints on the one side and 1.0 ml on theother side; subsequently she was completely symptom-free. It was notnecessary to repeat the treatment.

Application Example 2

[0020] Injections in the case of an extension of the hip joint resultedin an improvement following prior injection of 2 ml of local anaestheticonly for the purpose of the correct needle position, after 2 ml of thecollagen injection suspension according to example 5 had beeninfiltrated intraarticularly into each joint side. The observation timewas approximately two years. It was found that, above all, the initial,primary arthrotic complaints had come to a complete standstill after 6months.

[0021] Further similar case reports are available.

Application Example 3

[0022] Intraarticular injections of 1 ml of the collagen-containinginjection suspension according to example 3 brought about an approx. 70%improvement of the complaints according to the patient's statement inthe case of a left-side severe gonarthrosis. Since about 2 years, thecomplaints have remained constant.

1. Use of collagen for producing a drug for the treatment ofarthropathies, characterized in that the collagen is contained in aninjection suspension.
 2. Use according to claim 1 , characterized inthat the amount of the collagen contained in the injection suspension isabout 20 to 50 mg/ml.
 3. Use according to any of claims 1 or 2,characterized in that a local anaesthetic is also contained.
 4. Useaccording to claim 3 , characterized in that the amount of the localanaesthetic contained in the injection suspension is 1 to 5 mg/ml. 5.Use according to any of claims 1 to 4 , characterized in that thecollagen contained in the drug is collagen from bovine skin.